Is Akt activated by phosphorylation?

Akt phosphorylation triggers its activation. Liu et al. report that during cell cycle progression, under growth factor stimulation and DNA damage, Akt can be phosphorylated by cyclin A2/CDK2, mTORC2 and DNAPK. This new phosphorylation governs pS473 and pT308 to reach Akt activation.

What happens when Akt is phosphorylated?

Akt can phosphorylate and activate the IκB kinase IKKα, causing degradation of IκB and nuclear translocation of NF-κB where it promotes expression of caspase inhibitors, c-Myb and Bcl-xL.

How does phosphorylation affect serine?

Diagram of serine phosphorylation. Enzyme-catalyzed proton transfer from the (–OH) group on serine stimulates the nucleophilic attack of the γ-phosphate group on ATP, resulting in transfer of the phosphate group to serine to form phosphoserine and ADP.

What is phosphorylated Akt?

Phosphorylated Akt (p-Akt) was implicated in inducing signals to interfere with the cell apoptosis, and promoting abilities of proliferation and motility through a crucial mechanism, the activation of mTOR (mammalian target of rapamycin) [4, 5, 6].

How is the AKT pathway activated?

Akt activation is initiated when the translocated Akt is phosphorylated on T308 residue by membrane localized phosphoinositide-dependent kinase-1 (PDK-1). However, complete activation is achieved only when PDK2 the second phosphorylation site S473 is phosphorylated by rapamycin-insensitive mTORC2.

What activates Akt pathway?

Activation of Akt signaling pathway Activation of Akt can begin with several events, mainly the binding of a ligand to a receptor in the cell membrane. The most common ligands activating Akt include growth factors, cytokines, mitogens, and hormones.

What is the identity of the enzyme that phosphorylates serine 473 on Akt?

Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion.

What is the role of phosphorylation?

In eukaryotes, protein phosphorylation plays a key role in cell signaling, gene expression, and differentiation. Protein phosphorylation is also involved in the global control of DNA replication during the cell cycle, as well as in the mechanisms that cope with stress-induced replication blocks.

How does Akt activate mTOR?

The known pathway by which Akt activates mTOR is via direct phosphorylation and inhibition of tuberous sclerosis complex 2 (TSC2), which is a negative regulator of mTOR.

Which amino acids undergo phosphorylation?

Phosphorylation is found most commonly on specific serine and threonine amino acid residues in proteins, but it also occurs on tyrosine and other amino acid residues (histidine, aspartic acid, glutamic acid) as well.